Membrane protein structures are vastly underrepresented in structure databases in relation to their importance and prevalence in living organisms. The investigators propose to develop and integrate novel liquids and solids NMR methods and biochemical methods (disulfide crosslinking and thermodynamic measurements) to determine the structure of a large membrane protein for the first time. LH1 protein, a 200 kD hetero-oligomeric membrane protein from photoheterotrophic eubacteria, undergoes multiple reversible unfolding (dissociation) and folding (association) reactions, and is well-suited for high-resolution structure determination by liquids and solids NMR. The proposed studies represent an important methodological proof-of-concept that will encourage structural investigations on other membrane proteins with direct medical relevance. The goal of the liquids NMR experiments is to determine the structures of LH1 subcomplexes and to ascertain the degree to which the individual solution structures can be used to build up structures of the intact complex. The solids NMR experiments will be used to determine structures of subcomplexes and intact complexes in a variety of solvent conditions, with the goal of determining NMR signatures for assessing membrane protein folding (association). Liquids and solids NMR dynamics will be ascertained for side- chain and backbone motions on a variety of timescales and they will be compared for LH1 and its subcomplexes. The dynamics will be related to the disulfide crosslinking kinetics, and to the thermodynamics of association. The overall goal is to understand the relationship between structure, conformational dynamics, function and thermodynamic stability for membrane proteins.